1. Field of the Invention
The present invention generally relates to layered particle compositions and methods for controlled drug delivery and the use thereof for prevention and treatment of pathological conditions, such as cancer.
2. Description of Related Art
Combination chemotherapy represents a mainstay treatment modality essential for improvement of survival rates in many cancers as well as other disease conditions. However, despite numerous regimens employed clinically, patient responses following combination therapies, such as polychemotherapy, often remains dismal. Recent molecular insights into underlying signaling pathways and networks suggest that drug synergy in combination chemotherapy may be significantly enhanced if the order of administration, scheduling, and dose duration are given proper consideration.
However, while specific combinations of drugs delivered in a time-staggered fashion have been shown to synergistically enhance cell killing pre-clinically (e.g., in cell culture systems), this strategy has not translated successfully to the clinic. Pharmacokinetic limitations of conventional drug formulations, including short circulation half-lives and heightened volumes of distribution, result in non-specific accumulation of drugs in healthy tissues and insufficient bioavailability in tumors. Moreover, different routes of administration, as well as distinct excipients associated with individual formulations of conventional drugs, result in disparate pharmacokinetic parameters that preclude adherence to strict time constraints specifically in tumors, thereby negating therapeutic crosstalk between synergistic agents. Thus, there remains a need for methods (and delivery systems) that can provide sequenced and timed delivery of combinations of different therapeutic or imaging agents.